Investigation On The Risk Factors And The Mechanism Of Thromboembolic Events In ANCA Associated Vasculitis

Objective:The aim of this study is to analyze the clinical features and related risk factors of ANCA associated vasculitis complicated with thromboembolism events.In addition,we tried to investigate the expression of plasma endothelial microparticles(EMP)and platelet microparticles(PMP)in patients with AAV,and to explore the mechanism of microparticles in AAV complicated with thrombosis.Methods:The research is divided into two parts: clinical research and experimental research.1.Clinical research: Clinical information was retrospectively collected from patients diagnosed as ANCA associated vasculitis in The Affiliated Hospital of Qingdao University from January 2013 to December 2018.The patients were divided into embolic group and nonembolic group according to the presence or absence of thromboembolism.Logistic regression analysis was used to explore the risk factors of AAV patients complicated with thromboembolism.2.Experimental research: Plasma samples were collected from patients diagnosed as ANCA associated vasculitis in our hospital from January 2017 to October 2018,as well as membranous nephropathy,chronic nephritis and healthy people.Plasma EMP and PMP levels were measured by flow cytometry.SPSS22.0 statistical software was used for analysis.Results:1.Clinical results: Data of a total of 177 patients were collected.Compared with the non-embolization group,patients complicated with thromboembolism showed a significant statistical difference in acute infection,BVAS,serum creatinine,ESR,ddimer,platelet count,and C3?By multivariate logistic regression analysis,acute infection(OR 1.371;95%CI 1.253-12.398),C3(OR 0.029;95%CI 0.002-0.382),ESR(OR 1.015;95%CI 1.002-1.028)were independent risk factors for thromboembolism associated with AAV.History of the coronary heart disease(OR 3.128;95%CI 1.024-9.553)were independent risk factors for ATE associated with AAV,and lung involvement(OR 4.2199;95%CI 1.291-13.787),BVAS(OR 1.094;95% CI 1.005-1.191),the ESR(1.020;95%CI 1.002-1.038)were independent risk factors for VTE associated with AAV.In the embolization group,82.1% of patients were in the AAV active stage,17.9% in the remission stage,and 50% in the duration 2 months after the diagnosis.2.Experimental results:The plasma levels of EMP and PMP in AAV group were higher than those in nonembolization group(EMP 10.4 2.8%VS5.6 2.4%,PMP 16.3 7.9%VS8.6 3.9%),and EMP/PMP levels in active stage of AAV group were higher than those in remission group(EMP 6.5 2.3%VS4.7 2.2%,PMP 10.3 4.4%VS6.8 2.3%).Correlation analysis showed that the plasma level of EMP was positively correlated with the level of BVAS,CRP and d-dimer.PMP was positively correlated with the level of BVAS,ESR,CRP,d-dimer and platelet count.The plasma levels of EMP and PMP in the active AAV group were higher than those in the membranous nephropathy group,chronic nephritis group and healthy control group.Levels of EMP and PMP in the remission stage of AAV group were higher than those in the chronic nephritis group and healthy control group.Conclusion:Concomitant acute infection?the level of ESR and decreased C3 were independent risk factors for thromboembolism in AAV patients.The previous history of coronary heart disease was an independent risk factor for ATE in AAV patients;the level of BVAS,ESR and lung involvement were independent risk factors for patients with AAV complicated with VTE.Patients with AAV in active phrase are more prone to forming clots,especially in the duration 2 months after the diagnosis.The plasma levels of EMP and PMP in the AAV group with thromboembolism were obviously higher than those in the non-embolization group.The plasma levels of EMP and PMP can reflect the degree of vascular endothelial injury and platelet activation mediated by immune inflammation,and are related to the active inflammatory response and thrombosis of AAV disease.The events of thromboembolism are more likely to occur in the active phase than in the remission phrase.